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- W2267563552 abstract "Ikaros encodes a DNA binding protein that regulates gene expression via chromatin remodeling and epigenetic mechanisms. The loss of Ikaros activity due to genetic or functional inactivation results in the development of high-risk leukemia in humans. Our goal is to determine the mechanisms by which Ikaros regulates transcription in human leukemia. Previous studies showed that Ikaros function in leukemia is controlled through its direct phosphorylation by Casein Kinase II (CK2). Treatment of leukemia cells with CK2 inhibitors results in enhanced Ikaros activity, which leads to cessation of cell growth. We have studied the mechanism by which inhibition of CK2 regulates Ikaros-induced epigenetic changes in leukemia. The human Nalm6 pre-B cell leukemia was treated with CK2 inhibitor, and the epigenetic signature of the histone modifications H3K4me3 and H3K36me3 were determined using chromatin immunoprecipitation coupled with next generation sequencing (ChIP-SEQ). Both H4K4me3 and H3K36me3 histone modifications are associated with positive regulation of gene expression. The enrichment of a particular histone modification was confirmed by quantitative chromatin immunoprecipitation (qChIP). Our data demonstrate that the inhibition of CK2 activity in leukemia results in a marked alteration in the epigenetic signature of H3K4me3 and H3K36me3 as compared to untreated cells. This is directly related to altered Ikaros binding to its target genes following CK2 inhibition. Current bioinformatics analysis is directed toward establishing a link between epigenetic modifications and Ikaros binding in leukemia. These results suggest that CK2 and Ikaros regulate gene transcription in leukemia via histone modifications. Grant Funding Source: Supported by NIH R01 HL095120 (SD); NIHR21CA162259 (KP), St. Baldrick's Foundation Awards (SD,KP,CC)" @default.
- W2267563552 created "2016-06-24" @default.
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- W2267563552 date "2014-04-01" @default.
- W2267563552 modified "2023-09-23" @default.
- W2267563552 title "Regulation of the epigenetic signature in leukemia by Ikaros (800.5)" @default.
- W2267563552 doi "https://doi.org/10.1096/fasebj.28.1_supplement.800.5" @default.
- W2267563552 hasPublicationYear "2014" @default.
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